Sinulariolide is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinulariolide on A375 melanoma cell growth and protein expression. Sinulariolide suppressed the proliferation and migration of melanoma cells in a concentration-dependent manner and was found to induce both early and late apoptosis by flow cytometric analysis. Comparative proteomic analysis was conducted to investigate the effects of sinulariolide at the molecular level by comparison between the protein profiles of melanoma cells treated with sinulariolide and those without treatment. Two-dimensional gel electrophoresis (2-DE) master maps ofcontrol and treated A375 cells were generated by analysis with PDQuest software.
Comparison between these maps showed up- and downregulation of 21 proteins, seven of
which were upregulated and 14 were downregulated. The proteomics studies described
here identify some proteins that are involved in mitochondrial dysfunction and
apoptosis-associated proteins, including heat shock protein 60, heat shock protein beta-1,
ubiquinol cytochrome c reductase complex core protein 1, isocitrate dehydrogenase (NAD)
subunit alpha (down-regulated), and prohibitin (up-regulated), in A375 melanoma cells
exposed to sinulariolide. Sinulariolide-induced apoptosis is relevant to mitochondrial-mediated
apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial
membrane potential, release of cytochrome c, and activation of Bax, Bad and caspase-3/-9,
as well as suppression of p-Bad, Bcl-xL and Bcl-2. Taken together, our results show that
sinulariolide-induced apoptosis might be related to activation of the caspase cascade and
mitochondria dysfunction pathways. Our results suggest that sinulariolide merits further
evaluation as a chemotherapeutic agent for human melanoma
